Chapter 22
Lecture
Outline
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22-1
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Respiratory System
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Anatomy of the Respiratory System
Pulmonary Ventilation
Gas Exchange and Transport
Respiratory Disorders
22-2
General Aspects
• Airflow in lungs
– bronchi  bronchioles  alveoli
• Conducting division
– passages for airflow, nostrils to bronchioles
• Respiratory division
– distal gas-exchange regions, alveoli
• Upper respiratory tract
– organs in head and neck, nose through larynx
• Lower respiratory tract
– organs of thorax, trachea through lungs
22-3
Alveolar Blood Supply
22-4
Alveolus
Fig. 22.11
b and c
22-5
Pleurae and Pleural Fluid
• Visceral (on lungs) and parietal (lines rib
cage) pleurae
• Pleural cavity - space between pleurae,
lubricated with fluid
• Functions
– reduce friction
– create pressure gradient
• lower pressure assists lung inflation
– compartmentalization
• prevents spread of infection
22-6
Pulmonary Ventilation
• Breathing (pulmonary ventilation) – one
cycle of inspiration and expiration
(respiratory cycle)
– quiet respiration – at rest
– forced respiration – during exercise
• Flow of air in and out of lung requires a
pressure difference between air pressure
within lungs and outside body
22-7
Respiratory Muscles
• Diaphragm (dome shaped)
– contraction flattens diaphragm
• Scalenes - hold first pair of ribs stationary
• External and internal intercostals
– stiffen thoracic cage; increases diameter
• Pectoralis minor, sternocleidomastoid and
erector spinae muscles
– used in forced inspiration
• Abdominals and latissimus dorsi
– forced expiration (to sing, cough, sneeze)
22-8
Respiratory Muscles
22-9
Neural Control of Breathing
• Breathing depends on repetitive stimuli from
brain
• Neurons in medulla oblongata and pons control
unconscious breathing
• Voluntary control provided by motor cortex
• Inspiratory neurons: fire during inspiration
• Expiratory neurons: fire during forced expiration
• Fibers of phrenic nerve go to diaphragm;
intercostal nerves to intercostal muscles
22-10
Respiratory Control Centers
• Respiratory nuclei in medulla
– Ventral Respiratory Group- primary generator of the
respiratory rhythm
– Inspiratory neurons and expiratory neurons, p 877, 878
– Dorsal Respiratory Group, integrating center that
receives input from other areas (pons, cehmosensitive
area in medulla, peripheral chemoreceptors, and
stretch and irritant receptors
• Pons
– Pontine respiratory group
– Receives input from higher brain centers and
transmits signals to VRG and DRG that modify timing
of transition from inspiration to expiration
22-11
Respiratory Control Centers
22-12
Input to Respiratory Centers
• From limbic system and hypothalamus
– respiratory effects of pain and emotion
• From airways and lungs
– irritant receptors in respiratory mucosa
• stimulate vagal afferents to medulla, results in
bronchoconstriction or coughing
– stretch receptors in airways - inflation reflex
• excessive inflation triggers reflex
• stops inspiration
• From chemoreceptors
– monitor blood pH, CO2 and O2 levels
22-13
Chemoreceptors
• Peripheral chemoreceptors
– found in major blood vessels
• aortic bodies
– signals medulla by vagus nerves
• carotid bodies
– signals medulla by glossopharyngeal nerves
• Central chemoreceptors
– in medulla
• primarily monitor pH of CSF
22-14
Peripheral Chemoreceptor Paths
22-15
Voluntary Control
• Neural pathways
– motor cortex of frontal lobe of cerebrum sends
impulses down corticospinal tracts to
respiratory neurons in spinal cord, bypassing
brainstem
• Limitations on voluntary control
– blood CO2 and O2 limits cause automatic
respiration
22-16
Pressure and Flow
• Atmospheric pressure drives respiration
– 1 atmosphere (atm) = 760 mmHg
• Intrapulmonary pressure and lung volume
Boyle’s Law: pressure is inversely proportional
to volume
• for a given amount of gas, as volume , pressure 
and as volume , pressure 
• Pressure gradients
– difference between atmospheric and
intrapulmonary pressure
– created by changes in volume thoracic cavity22-17
Inspiration
Put your hands on your rib cage. Inhale. Notice
that the thoracic cage moves up and out.
Diaphragm moves down (Fig 22-8, A and C
Herlihy)
• This movement increases the volume of
the thoracic cavity and lungs.
• As the volume in the lung increases, the
pressure in the lung decreases (Boyle’s
Law)
• P in the lung < atmospheric P so air flows
22-18
in
Respiratory Cycle
22-19
Passive Expiration
• During quiet breathing, expiration achieved
by elasticity of lungs and thoracic cage
• Diaphragm relaxes, moves up. Rib cage
moves down and in.
• As volume of thoracic cavity ,
intrapulmonary pressure  and air is
expelled
22-20
Forced Expiration
• Internal intercostal muscles
– depress the ribs
• Contract abdominal muscles
–  intra-abdominal pressure forces
diaphragm upward
–  pressure on thoracic cavity
22-21
Pneumothorax
• Presence of air in pleural cavity
– loss of negative intrapleural pressure allows
lungs to recoil and collapse
• Collapse of lung (or part of lung) is called
atelectasis
22-22
Resistance to Airflow
the greater the resistance, the slower the flow
• Pulmonary compliance
– The ease with which the lungs expand
– change in lung volume relative to a change in
transpulmonary pressure
• Bronchiolar diameter
– primary control over resistance to airflow
– Bronchoconstriction (reduce airflow)
• triggered by airborne irritants, cold air,
parasympathetic stimulation, histamine
– Bronchodilation (increase airflow)
• sympathetic nerves, epinephrine
22-23
Alveolar Surface Tension
• Thin film of water needed for gas exchange
– creates surface tension that acts to collapse
alveoli and distal bronchioles
• Pulmonary surfactant (great alveolar cells)
– decreases surface tension
• Premature infants that lack surfactant
suffer from respiratory distress syndrome
22-24
Alveolar Ventilation
• Dead air
– fills conducting division of airway, cannot
exchange gases
• Anatomic dead space
– conducting division of airway
• Physiologic dead space
– sum of anatomic dead space and any
pathological alveolar dead space
• Alveolar ventilation rate
– air that ventilates alveoli X respiratory rate
– directly relevant to ability to exchange gases 22-25
Measurements of Ventilation
• Spirometer - measures ventilation
• Respiratory volumes
– tidal volume: volume of air in one quiet breath
– inspiratory reserve volume
• air in excess of tidal inspiration that can be inhaled
with maximum effort
– expiratory reserve volume
• air in excess of tidal expiration that can be exhaled
with maximum effort
– residual volume (keeps alveoli inflated)
• air remaining in lungs after maximum expiration
22-26
Lung Volumes and Capacities
22-27
Respiratory Capacities
• Vital capacity
– total amount of air that can be exhaled with
effort after maximum inspiration
• assesses strength of thoracic muscles and
pulmonary function
• Inspiratory capacity
– maximum amount of air that can be inhaled
after a normal tidal expiration
• Functional residual capacity
– amount of air in lungs after a normal tidal
expiration
22-28
Respiratory Capacities
• Total lung capacity
– maximum amount of air lungs can hold
• Forced expiratory volume (FEV)
– % of vital capacity exhaled/ time
– healthy adult - 75 to 85% in 1 sec
• Peak flow
– maximum speed of exhalation
• Minute respiratory volume (MRV)
– TV x respiratory rate, at rest 500 x 12 = 6 L/min
– maximum: 125 to 170 L/min
22-29
Respiratory Volumes and Capacities
• Age -  lung compliance, respiratory muscles
weaken
• Restrictive disorders
–  compliance and vital capacity (limit amt
lungs can be inflated)
• Obstructive disorders
– interfere with airflow by narrowing or blocking
the airway
22-30
Composition of Air
• Dalton’s Law: total atmospheric pressure is a sum of the
contributions of the individual gases
• Mixture of gases; each contributes its
partial pressure
– at sea level 1 atm. of pressure = 760 mmHg
– nitrogen constitutes 78.6% of the atmosphere so
• PN2 = 78.6% x 760 mmHg = 597 mmHg
• PO2 =
159
• PH2O =
3.7
• PCO2 =
+ 0.3
• PN2 + PO2 + PH2O + PCO2 = 760 mmHg
22-31
Composition of Air
• Partial pressures (as well as solubility of gas)
– determine rate of diffusion of each gas and
gas exchange between blood and alveolus
• Alveolar air
– humidified, exchanges gases with blood, mixes with
residual air
– contains:
• PN2 = 569
• PO2 = 104
• PH2O = 47
• PCO2 = 40 mmHg
22-32
Air-Water Interface
• Important for gas exchange between air
in lungs and blood in capillaries
• Gases diffuse down their concentration
gradients
• Henry’s law
– amount of gas that dissolves in water is
determined by its solubility in water and its
partial pressure in air
22-33
Alveolar Gas Exchange
22-34
Alveolar Gas Exchange
• Time required for gases to equilibrate =
0.25 sec
• RBC transit time at rest = 0.75 sec to pass
through alveolar capillary
• RBC transit time with vigorous exercise =
0.3 sec
22-35
Factors Affecting Gas Exchange
• Concentration gradients of gases
– PO2 = 104 in alveolar air versus 40 in blood
– PCO2 = 46 in blood arriving versus 40 in
alveolar air
• Gas solubility
– CO2 20 times as soluble as O2
• O2 has  conc. gradient, CO2 has 
solubility
22-36
Factors Affecting Gas Exchange
• Membrane thickness - only 0.5 m thick
• Membrane surface area - 100 ml blood in
alveolar capillaries, spread over 70 m2
• Ventilation-perfusion coupling - areas of
good ventilation need good perfusion
(vasodilation)
22-37
Concentration Gradients of Gases
22-38
Ambient Pressure and Concentration
Gradients
22-39
Lung Disease Affects Gas Exchange
22-40
Perfusion Adjustments
22-41
Ventilation Adjustments
22-42
Oxygen Transport
• Concentration in arterial blood
– 20 ml/dl
• 98.5% bound to hemoglobin
• 1.5% dissolved
• Binding to hemoglobin
– each heme group of 4 globin chains may
bind O2
– oxyhemoglobin (HbO2 )
– deoxyhemoglobin (HHb)
22-43
Oxygen Transport
• Oxyhemoglobin dissociation curve
– relationship between hemoglobin saturation
and PO2 is not a simple linear one
– after binding with O2, hemoglobin changes
shape to facilitate further uptake (positive
feedback cycle)
22-44
Oxyhemoglobin Dissociation Curve
22-45
Carbon Dioxide Transport
• As carbonic acid - 90%
– CO2 + H2O  H2CO3  HCO3- + H+
• As carbaminohemoglobin (HbCO2)- 5% binds to
amino groups of Hb (and plasma proteins)
• As dissolved gas - 5%
• Alveolar exchange of CO2
– carbonic acid - 70%
– carbaminohemoglobin - 23%
– dissolved gas - 7%
22-46
Systemic Gas Exchange
• CO2 loading
– carbonic anhydrase in RBC catalyzes
• CO2 + H2O  H2CO3  HCO3- + H+
– chloride shift
• keeps reaction proceeding, exchanges
HCO3- for Cl- (H+ binds to hemoglobin)
• O2 unloading
– H+ binding to HbO2  its affinity for O2
• Hb arrives 97% saturated, leaves 75%
saturated - venous reserve
– utilization coefficient
• amount of oxygen Hb has released 22%
22-47
Systemic Gas Exchange
22-48
Alveolar Gas Exchange Revisited
• Reactions are reverse of systemic gas
exchange
• CO2 unloading
– as Hb loads O2 its affinity for H+ decreases, H+
dissociates from Hb and bind with HCO3• CO2 + H2O  H2CO3  HCO3- + H+
– reverse chloride shift
• HCO3- diffuses back into RBC in exchange
for Cl-, free CO2 generated diffuses into
alveolus to be exhaled
22-49
Alveolar Gas Exchange
22-50
Factors Affect O2 Unloading
• Active tissues need oxygen!
– ambient PO2: active tissue has  PO2 ; O2 is
released
– temperature: active tissue has  temp; O2 is
released
– Bohr effect: active tissue has  CO2, which
lowers pH O2 is released
22-51
Oxygen Dissociation and Temperature
22-52
Oxygen Dissociation and pH
Bohr effect: release of O2 in response to low pH
22-53
Factors Affecting CO2 Loading
• Haldane effect
– low level of HbO2 (as in active tissue) enables
blood to transport more CO2
– HbO2 does not bind CO2 as well as
deoxyhemoglobin (HHb)
– HHb binds more H+ than HbO2
• as H+ is removed this shifts the
CO2 + H2O  HCO3- + H+
reaction to the right
22-54
Blood Chemistry
and Respiratory Rhythm
• Rate and depth of breathing adjusted to
maintain levels of:
– pH
– PCO2
– PO2
• Let’s look at their effects on respiration:
22-55
Effects of Hydrogen Ions
• pH of CSF (most powerful respiratory stimulus)
• Respiratory acidosis (pH < 7.35) caused by
failure of pulmonary ventilation
– hypercapnia: PCO2 > 43 mmHg
• CO2 easily crosses blood-brain barrier
• in CSF the CO2 reacts with water and releases H+
• central chemoreceptors strongly stimulate
inspiratory center
– “blowing off ” CO2 pushes reaction to the left
CO2 (expired) + H2O  H2CO3  HCO3- + H+
– so hyperventilation reduces H+ (reduces acid) 22-56
Effects of Hydrogen Ions
• Respiratory alkalosis (pH > 7.45)
– hypocapnia: PCO2 < 37 mmHg
– Hypoventilation ( CO2), pushes reaction to the
right
 CO2 + H2O  H2CO3  HCO3- + H+
–  H+ (increases acid), lowers pH to normal
• pH imbalances can have metabolic causes
– uncontrolled diabetes mellitus
• fat oxidation causes ketoacidosis, may be
compensated for by Kussmaul respiration
(deep rapid breathing)
22-57
Effects of Carbon Dioxide
• Indirect effects on respiration
– through pH as seen previously
• Direct effects
–  CO2 may directly stimulate peripheral
chemoreceptors and trigger  ventilation more
quickly than central chemoreceptors
22-58
Effects of Oxygen
• Usually little effect
• Chronic hypoxemia, PO2 < 60 mmHg,
can significantly stimulate ventilation
– emphysema, pneumonia
– high altitudes after several days
22-59
Hypoxia
• Causes:
– hypoxemic hypoxia - usually due to
inadequate pulmonary gas exchange
• high altitudes, drowning, aspiration, respiratory
arrest, degenerative lung diseases, CO poisoning
– ischemic hypoxia - inadequate circulation
– anemic hypoxia - anemia
– histotoxic hypoxia - metabolic poison (cyanide)
• Signs: cyanosis - blueness of skin
• Primary effect: tissue necrosis, organs with
high metabolic demands affected first
22-60
Oxygen Excess
• Oxygen toxicity: pure O2 breathed at 2.5
atm or greater
– generates free radicals and H2O2
– destroys enzymes
– damages nervous tissue
– leads to seizures, coma, death
• Hyperbaric oxygen
– formerly used to treat premature infants,
caused retinal damage, discontinued
22-61
Chronic Obstructive Pulmonary Disease
• Asthma
– allergen triggers histamine release
– intense bronchoconstriction (blocks air flow)
• Other COPD’s usually associated with smoking
– chronic bronchitis
– emphysema
22-62
Chronic Obstructive Pulmonary Disease
• Chronic bronchitis
– cilia immobilized and  in number
– goblet cells enlarge and produce excess
mucus
– sputum formed (mucus and cellular debris)
• ideal growth media for bacteria
– leads to chronic infection and bronchial
inflammation
22-63
Chronic Obstructive Pulmonary Disease
• Emphysema (barrel chest)
– alveolar walls break down
• much less respiratory membrane for gas exchange
– healthy lungs are like a sponge; in emphysema, lungs are
more like a rigid balloon
– lungs fibrotic and less elastic
– air passages collapse
• obstruct outflow of air
• air trapped in lungs
22-64
Effects of COPD
•  pulmonary compliance and vital capacity
• Hypoxemia, hypercapnia, respiratory
acidosis
– hypoxemia stimulates erythropoietin release
and leads to polycythemia
• cor pulmonale
– hypertrophy and potential failure of right heart
due to obstruction of pulmonary circulation
22-65
Smoking and Lung Cancer
• Lung cancer accounts for more deaths
than any other form of cancer
– most important cause is smoking (15
carcinogens)
• Squamous-cell carcinoma (most common)
– begins with transformation of bronchial
epithelium into stratified squamous
– dividing cells invade bronchial wall, cause
bleeding lesions
– dense swirls of keratin replace functional
respiratory tissue
22-66
Lung Cancer
• Adenocarcinoma
– originates in mucous glands of lamina propria
• Small-cell (oat cell) carcinoma
– least common, most dangerous
– originates in primary bronchi, invades
mediastinum, metastasizes quickly
22-67
Progression of Lung Cancer
• 90% originate in primary bronchi
• Tumor invades bronchial wall, compresses
airway; may cause atelectasis
• Often first sign is coughing up blood
• Metastasis is rapid; usually occurs by time
of diagnosis
– common sites: pericardium, heart, bones,
liver, lymph nodes and brain
• Prognosis poor after diagnosis
– only 7% of patients survive 5 years
22-68
Healthy Lung/Smokers Lung- Carcinoma
22-69